This project endeavors to provide safe non-invasive, but powerful imaging methods for studying pulmonary physiology and diagnosing and evaluating lung diseases. One aim is to develop a new method of imaging alveolar ventilation to blood perfusion ratios (VA/Qs). The spatial distribution of this ratio is of central diagnostic importance in obstructive lung disease and characterizes the lung's ability to exchange gas. An advantage of our new method over our prior one is that patients who regularly breath oxygen enriched air will not have to breath gas with normal oxygen concentrations, but can breath a mixture rich in oxygen the entire time. The method will be developed in laboratory rats. Specifically, it involves imaging the longitudinal nuclear magnetic relaxation time of an inert fluorinated gas, which we recently discovered is a monotonic function of VA/Q. Because it will quantify VA/Qs in the low range that cause poor arterial blood gases, it is not only potentially a diagnostic tool but also a tool for advancing the physiology of gas exchange in diseased and normal individuals. After development, both VA/Q imaging methods will be applied to a study of elastase induced emphysema in rats. A second aim is to systematically develop methods to detect magnetic particles in images of inert fluorinated gas. The methods will be applied to collaborative studies of the patterns of deposition of magnetically labeled aerosol particles in rat lungs and the invasion of transplanted rat lungs by magnetically labeled immune cells. Understanding of how and where aerosol particles deposit in lungs is important to advancing the toxicology of inhaled air pollution and can further the effectiveness of inhaled drugs. Imaging lung rejection is important to diagnosing acute rejection and studying the rejection process to develop improved immunosuppressive strategies. Specifically, we will tailor methods of detecting magnetic particles in gas images for use in our collaborator's animal models and laboratories by systematic exploitation of the frequency shift and diffusional signal loss contrast mechanisms. With this second aim, we will advance inert fluorinated gas imaging beyond a development and demonstration stage to a new research tool that provides previously unavailable data to medical research.